The long term goals are to study the regulation of neuronal transmission in the central nervous system and to understand the role of pharmacological agents in modifying neuronal transmission. The current proposal to clone the catecholamine uptake transmitter reflects to the application of basic science to clinical issues . The importance of catecholamine uptake transporters is demonstrated by the impact in our society of specific inhibitors of these proteins, namely cocaine, amphetamines, and tri-cyclic antidepressants. 'Me stimulatory action and abuse potential is directly related to their ability to bind and block catecholamine uptake at the presynaptic nerve terminals. To study the pharmacology of cocaine and to understand the molecular basis for its medical effects, it is necessary to isolate and characterize the transporter proteins themselves. Molecular cloning of catecholamine transporters is the most direct way to gain access to this class of transporters. Their ability to bind inhibitors with high affinity and to concentrate catecholamines within a cell make these proteins ideally suited to molecular cloning by expression in heterologous cells. This application presents a cloning strategy employing radiolabelled ligands and substrates to isolate the cDNA encoding a catecholamine transporter following its expressing in COS cells.